Thiolate ions addition

Even though the high carbon basicity of thiolate ion nucleophiles is a major reason why their nucleophilic reactivity is much higher than that of oxyanions or amines of comparable pATa, there is an added effect that comes from a reduced intrinsic barrier. For example, intrinsic rate constants for thiolate ion addition to a-nitrostilbene or p-nitrostyrene are up to 100-fold higher than for amine addition. This has been explained in terms of the soft soft interaction... 

The intrinsic rate constants for thiolate ion addition to 76-Cr and 76-W are substantially larger than those for alkoxide ion addition. This is similar to the previously mentioned higher intrinsic reactivity of thiolate ions compared to amine nucleophiles for the addition to a-nitrostilbene and p-nitrostyrene. It can be understood in terms of the soft-soft interaction of the thiolate ion with the carbene complex which is more advanced than C S bond formation at the transition state.184... 

The conversion of a thiolactone to a cyclic ether can also be used as a key step in the synthesis of functionalized, stereochemically complex oxacycles (see 64—>66, Scheme 13). Nucleophilic addition of the indicated higher order cuprate reagent to the C-S double bond in thiolactone 64 furnishes a tetrahedral thiolate ion which undergoes smooth conversion to didehydrooxepane 65 upon treatment with 1,4-diiodobutane and the non-nucleophilic base 1,2,2,6,6-pentamethylpiperidine (pempidine).27 Regio- and diastereoselective hydroboration of 65 then gives alcohol 66 in 89 % yield after oxidative workup. Versatile vinylstannanes can also be accessed from thiolactones.28 For example, treatment of bis(thiolactone) 67 with... 

The experiments with 2-(3-butenyloxy)benzenediazonium ions (10.55, Z = 0, n = 2, R=H) and benzenethiolate showed a significant shift of the product ratio in favor of the uncyclized product 10.57. They also indicated that the covalent adduct Ar — N2 — SC6H5 is formed as an intermediate, which then undergoes homolytic dissociation to produce the aryl radical (Scheme 10-83). Following the bimolecular addition of the aryl radical to a thiolate ion (Scheme 10-84), the chain propagation reaction (Scheme 10-85) yielding the arylphenylsulfide is in competition with an alternative route leading to the uncyclized product 10.57. 

The Ad -E mechanism proposed to account for the kinetics of substitution of 9-(a-bromo-a -arylmethylene)fluorenes by thiolate ions in aqueous acetonitrile also features elimination of the leaving group in a fast step following rate-determining carbanion formation (by nucleophilic addition). ... 

Whereas it has been demonstrated that both malonate ions and thiolate ions can catalyze the free radical chain addition reaction of perfluoroalkyl iodides to olefins [289,290], under appropriate conditions one can obtain products deriving from substitution in such processes. Following early work carried out photo-lytically in liquid ammonia, recent reports have indicated that good yields of substitution products can be obtained in polar solvents at room temperature, without irradiation [291-296]. 

In contrast to the observed reactivity of phenoxide and aryl alkoxide ions, arene and heteroarene thiolate ions typically couple with aryl radical to generate C—S bonds. The only exception to this regioselective reaction is the addition of 1-naphthalene thiolate ion to p-anisyl radical to render both C- and S-substitutions in 14% and 65% yields, respectively, while with 1-naphthyl radical, 95% of C—S coupling is obtained. In general, PhS- ions react with Arl in liquid ammonia under photostimulation to afford good yields of ArSPh or heteroaryl-SAr (70-100%). Substitution of the less-reactive ArBr can be achieved under photochemical initiation in DMF, MeCN, or DM SO [1],... 

The most common reaction of 2,4-bis-(methylene)-l,3-dithietanes with nucleophiles involves an apparent Michael addition to an electron-deficient double bond followed by ring-opening. Further reactions may ensue depending on the functional groups present. The reactions of 578 have been extensively investigated. Reactions have been reported with ethoxide ion and thiolate ions, ammonia and amines " " - (e.g., the formation of 579), hydra-... 

Boyer et al.(C. Boyer, J.J. Robin, B. Boutevin, unpublished results) used the nucleophilic addition of thiolate onto the double bond of alkyl (meth)acrylate to obtain monodispersed telechelic oligomers. This method is based on the nucleophilic character of the thiolate ion in the presence of a monomer carrying two acrylate or methacrylate functions to obtain the corresponding telechelic oligomers. The nucleophilic addition of the thiolate ion onto the double bond is quantitative (Scheme 4). 

This enhanced reactivity difference for thiolate addition has been attributed to the combination of two factors. The first is the favorable soft acid-soft base interaction for the reaction of the soft carbene complex with the soft thiolate ion which contrasts with the unfavorable hard acid (CH3COH)-soft base (EtS ) interaction in reaction (66). The second is the favorable hard acid-hard base interaction between the hard MeO with the hard methylbenzoate which contrasts with the unfavorable soft acid-hard base interaction in the reaction of the carbene complex with MeO. ... 

These results may be understood in the context of soft-hard acid-base theory.As mentioned earlier, the Fischer carbene complexes can be regarded as soft electrophiles, especially the alkylthio complexes. Hence, the adducts 99 formed by the reaction of 98b with a thiolate ion nucleophile enjoy enhanced stability due to the symbiotic effect of adding a soft nucleophile. This stabilization apparently reduces the need for additional stabilization by the phenyl substituent, which translates to a reduced p(Ki) value. 

The carbonyl carbon of a thioester is more susceptible to nucleophilic attack than is the carbonyl carbon of an oxygen ester because there is less electron delocalization onto the carbonyl oxygen when Y is S than when Y is O. There is less electron delocalization because there is less overlap between the 3p orbital of sulfur and the Ip orbital of carbon, compared with the amount of overlap between the Ip orbital of oxygen and the Ip orbital of carbon (Section 17.2). In addition, a thiolate ion is a weaker base and therefore a better leaving group than an alkoxide ion. 

Subsequent research showed the SrnI mechanism to occur with many other aromatic compounds. The reaction was found to be initiated by solvated electrons, by electrochemical reduction, and by photoinitiated electron transferNot only I, but also Br, Cl, F, SCeHs, N(CH3)3, and 0P0(0CH2CH3)2 have been foimd to serve as electrofuges. In addition to amide ion, phosphanions, thiolate ions, benzeneselenolate ion (C HsSe"), ketone and ester enolate ions, as well as the conjugate bases of some other carbon acids, have been identified as nucleophiles. The SrnI reaction was observed with naphthalene, phenanthrene, and other polynuclear aromatic systems, and the presence of alkyl, alkoxy, phenyl, carboxylate, and benzoyl groups on the aromatic ring does not interfere with the reaction. ... 

The highly reactive /3-propiolactone displays discriminatory reaction modes toward bases of different softness. For example, the hard alkoxide ion opens the lactone ring via addition to the acyl carbon (82) whereas the soft cyanide (83) and thiolate ions (84) effect displacement at the P carbon. Indole is alkylated at its P position to give 3-( -indolyl)propionic acid (85). 

The products of the reactions of thiols or thiolate ions with alkylene oxides may correspond to addition across the C—O bond, or reactions of the isomeric aldehyde or ketone if the temperature is sufficiently high. Simple addition is observed in reactions such as... 

The following arguments may rationalize the fact that inactivation is greatest near pH 4 (Friedman et al., 1982 d). Generally, nucleophilic addition of a thiol to a double bond, as in pathway 1, Figure 7, is proportional to the ionized thiolate ion (RS ). The concentration of this ion in solution is governed by pH. As a result, the rate of inactivation would be expected to be directly proportional to pH, as previously found for addition of thiols to the double band of vinyl compounds such as acrylonitrile (Friedman et al., 1965). 

Harder nucleophiles often react with thiirans to give a predominance of attack at carbon, with consequent cleavage of the weak carbon-sulphur bond. This strategy has been used to prepare 7-oxa-4-thia-alk-l-enes from alkoxides, thiiran, and allyl chlorides, yS-mercaptoethyl sulphides from thiiran and thiolate ions, thiazines by the CujO-catalysed cyclization of the adducts of a-lithio-isocyanides with thiirans, tautomeric mixtures of (18) and (19) or (20) from thiiran and hydrazones, 7V-methylpyrrolidines from bis(epithio)linoleic acid and methylamine, and 2,4-dimethylhex-5-ene-2-thiol by addition of the Grignard reagent derived from 3-chlorobut-l-ene with 2,2-dimethylthiiran. Methylthiiran has been found to open... 

Study of structure-activity relationships in nucleophilic vinylic substitution reactions (S nV) that proceed by the addition-elimination mechanism has been furthered by the study of acid-catalysed breakdown of alkoxide and thiolate ion adducts of benzylidene Meldrum s acid (36a), methoxybenzylidene Meldrum s acid (36b), and thiomethoxybenzylidene Meldrum s acid (36c). Catalysis of alkoxide or thiolate expulsion is in competition with protonation of the a-carbon or one of the carbonyl oxygens to form an enolate. The positive Ag values for H+-catalysed RO and RS departure imply an imbalanced transition state in which proton transfer leads C-O or C-S bond cleavage. The pA values of the various adducts are much lower than for Meldrum s acid, in view of the stabilizing influence of OR, SR, and OMe groups on the carbanion. 

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